Various polymer- and ceramic-based scaffolds have been studied for use as bone substitute compositions and for the purpose of bone regeneration. These scaffolds include hydroxyapatite (HA)-based ceramics and calcium phosphate cements (CPCs). CPCs are generally moldable, putty-like compounds that can be easily introduced into a defective bone site. They typically set within a period of time at normal body temperatures to form mechanically stable, osteo-conductive or osteo-inductive materials. Additionally, CPCs convert into natural bone-like calcium-deficient hydroxyapatite (CDHA) in vivo making them attractive for bone tissue engineering. Currently used CPCs have a relatively long setting time, for example, in excess of several tens of minutes, slow conversion, low resorption rates and low bone regeneration rates. CPCs would be more attractive for clinical applications if they exhibited enhanced resorption-degradation characteristics in vivo.
Further, the polymer and ceramic cement-based scaffolds that are known in the art for use as bone substitute compositions are generally not amenable for in situ incorporation of cells, growth factors and/or biological systems. This may be due, at least in part, to the harsh reaction conditions or reagents that are used and may be toxic to cells and biological systems. Hence, as a result, the cellular or biological components could be incorporated into the pre-fabricated system which would not allow one to substantially control the amount, distribution and homogeneity of the delivery agents. Further, the acidic or basic degradation products could also prove to be harmful to the cells or biological molecules added to the pre-fabricated system.
Reconstructive surgery in recent years has focused intensely on tissue repair and regeneration, in an attempt to overcome the limitations of the current treatment strategies. Artificial tissue substitutes have significantly assisted surgeons in the restoration of the form and, partly, the function of defective bones. In this context, the implementation of bioresorbable scaffolds have been regarded as an optimal model for tissue regeneration.
There is a need in the art to design and develop bone substitute compositions which can be generated under physiological conditions of neutral pH and may demonstrate the ability to contain nano-carriers of calcium phosphate that are complexed to cellular and/or biological materials, such as DNA, growth factors, cells and proteins. Additionally, it is desired for bone substitute compositions to have a reasonably short setting time, a reasonably rapid conversion time and relatively high resorption and bone regeneration rates.
Further, it is desired for bone substitute compositions to have relatively short initial setting times and relatively short final setting times; improved porosity of the CPCs, i.e. increased number and size of the pores inside the cement to accelerate bone tissue infiltration; increased exposed area to lead to greater resorption rates; and the ability to directly incorporate various cellular and/or biological materials in the developed apatitic-CPC to induce rapid bone regeneration around a defective bone site. Furthermore, it is desired that the incorporation of porosity, various cellular and/or biological materials including carriers of DNA, growth factors, proteins, and drugs, not impact the setting characteristics and mechanical properties of the bone substitute composition.